Experimental animals were studied under gnotobiotic conditions or in isolation to evaluate virulence of selected human and animal rotavirus strains as well as to study homologous and heterologous immunity. Studies were performed primarily in gnotobiotic piglets and rhesus monkeys. Three potential vaccines or vaccine precursors (human rotavirus strain D, bovine rotavirus UK and rhesus rotavirus MMU18006) were evaluated in gnotobiotic piglets. Infection in the absence of dehydrating diarrheal illness occurred following challenge with the human D strain and rhesus rotavirus. The UK bovine rotavirus did not cause disease; its capacity to infect piglets is not known at this time but this question will be answered when serologic studies are completed. These three strains will be studied further as potential vaccines. A member of the 4th human rotavirus serotype was also administered to gnotobiotic piglets; infection without dehydrating diarrheal illness was also observed. Prior exposure to rhesus rotavirus (serotype 3) appeared to decrease viral shedding following later challenge with human rotavirus strain M (serotype 3). Rhesus rotavirus MMU18006 was also administered to juvenile rhesus monkeys and did not produce disease, although serologic evidence of infection was demonstrated. Additional safety testing of this strain to rule out the presence of an agent which produces acquired immune deficiency in rhesus monkeys is under way. In a previous study of heterologous immunity, we demonstrated that in utero inoculation with bovine rotavirus protected calves against challenge with human rotavirus of a distinct serotype. Reevaluation of the calf sera and fecal samples from this study indicated that a single in utero exposure to bovine rotavirus induced broadly reactive neutralizing antibody and significantly diminished the viral shedding pattern on subsequent challenge with human rotavirus (strain D); this may explain the observed heterologous immunity.